Gas removal device for cryogenic freezing bags

ABSTRACT

This document relates to methods and materials for improving the removal of gas from cryogenic freezing bags. For example, this document describes methods and devices for restricting air paths within the cryogenic freezing bag.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Utility application Ser. No.16/518,244, filed Jul. 22, 2019, which claims the benefit of U.S.Provisional Application Ser. No. 62/702,658, filed Jul. 24, 2018. Thedisclosures of the prior applications are considered part of (and areincorporated by reference in) the disclosure of this application.

BACKGROUND 1. Technical Field

This document relates to methods and materials for improving the removalof gas from cryogenic freezing bags. For example, this document relatesto methods and devices for restricting air paths within the cryogenicfreezing bag.

2. Background Information

Cryogenic freezing bags can be used for cryo-preservation and/orcryo-conservation, which is a process where organelles, cells, tissues,extracellular matrix, organs or any other biological constructssusceptible to damage caused by unregulated chemical kinetics arepreserved by cooling to very low temperatures (e.g., −80° C. using solidcarbon dioxide or −196° C. using liquid nitrogen). Cryogenic freezingbags allow for the storage, preservation, and transfers of cells and/ortissues when using cryo-preservation and/or cryo-conservation.

Often when using cryo-preservation and/or cryo-conservation, acryoprotectant is used. A cryoprotectant is a substance used to protectbiological tissue from damage when frozen.

SUMMARY

This document relates to methods and materials for improving the removalof gas from cryogenic freezing bags. For example, this documentdescribes methods and devices for restricting air paths within thecryogenic freezing bag.

In one aspect, this disclosure is directed to a clamping device forremoving gas from a cryogenic freezing bag. The clamping device caninclude a first clamping element, and a second clamping element. Thefirst clamping element can include a first coupling portion defining afirst handle portion at a first proximal portion, a first side armextending from a first distal portion of the first coupling portion in afirst direction, wherein the first side arm defines a first recess, anda second side arm extending from the first distal portion the firstcoupling portion in a second direction different from the firstdirection, wherein the second side arm defines a first protrusion. Thesecond clamping element can include a second coupling portion defining asecond handle portion at a second proximal portion, a third side armextending from a second distal portion of the second coupling portion ina third direction, wherein the third side arm defines a secondprotrusion, and a fourth side arm extending from the second distalportion the second coupling portion in a fourth direction different fromthe third direction, wherein the fourth side arm defines a secondrecess. The first clamping element and the second clamping element canbe pivotally coupled along the first coupling portion between the firstproximal portion and the first distal portion and the second couplingportion between the second proximal portion and the second distalportion, such that movement of the first handle portion towards thesecond handle portion causes mating of the first protrusion with thesecond recess and the second protrusion with the first recess.

In some cases, the first coupling portion can define a first centralopening extending between the first side arm and the second side arm,and the second coupling portion can define a second central openingextending between the third side arm and the fourth side arm, such thatthe first central opening and the second central opening can receive atube of the cryogenic freezing bag. In some cases, the clamping devicefurther includes a locking mechanism to lock the first clamping elementand the second clamping element together. In some cases, the firstrecess and the second protrusion can be complementary of one another,and the second recess and the first protrusion can be complementary ofone another. In some cases, a first angle between the first directionand the second direction can be substantially similar to a second anglebetween the third direction and the fourth direction. In some cases, thefirst recess can extend along a first longitudinal axis of the firstside arm, the first protrusion can extend along a second longitudinalaxis of the second side arm, the second protrusion can extend along athird longitudinal axis of the third side arm, and the second recess canextend along a fourth longitudinal axis of the fourth side arm.

In another aspect, this disclosure is directed to a clamp element for ahemostat for removing gas from a cryogenic freezing bag. The clampelement can include a coupling portion configured to be coupled to thehemostat, a first side arm extending from the coupling portion in afirst direction, wherein the first side arm defines a recess, and asecond side arm extending from the coupling portion in a seconddirection different from the first direction, wherein the second sidearm comprises a protrusion.

In some cases, the coupling portion can define an aperture that cancouple to the hemostat. In some cases, the aperture can be at an angleoffset from a longitudinal axis of the coupling portion. In some cases,the coupling portion can define a central opening extending between thefirst side arm and the second side arm, the central opening configuredto receive a tube of the cryogenic freezing bag. In some cases, theclamping element can include a locking mechanism to lock the clampelement to a second clamp element. In some cases, the recess and theprotrusion can be complementary of one another, such that the recesscould receive the protrusion. In some cases, an angle between the firstdirection and the second direction can be about 110 degrees to about 180degrees. In some cases, the recess can extend along a longitudinal axisof the first side arm, and the protrusion can extend along alongitudinal axis of the second side arm.

In yet another aspect, this disclosure is directed to a method ofremoving g gas from a cryogenic freezing bag. The method can includeclamping a clamping device on the cryogenic freezing bag, the clampingdevice comprising a first clamping element and a second clampingelement, and removing gas from the cryogenic freezing bag.

In some cases, the method can include attaching the first clampingelement to a first tip of a hemostat, and attaching the second clampingelement to a second tip of the hemostat. In some cases, each of thefirst clamping element and the second clamping element can include acoupling portion configured to be coupled to the hemostat, a first sidearm extending from the coupling portion in a first direction, where thefirst side arm defines a recess, and a second side arm extending fromthe coupling portion in a second direction different from the firstdirection, where the second side arm comprises a protrusion. In somecases, clamping the clamping device on the cryogenic freezing bag caninclude sealing a first opening of the cryogenic freezing bag. In somecases, the first opening can be a spike port of the cryogenic freezingbag. In some cases, the method can include locking a locking mechanismof the clamping device.

Particular embodiments of the subject matter described in this documentcan be implemented to realize one or more of the following advantages.

As a result of a toxicity of a cryoprotectant mixture which containsDimethyl Sulfoxide (DMSO), and an attempt to preserve cell viability,devices and methods described herein can reduce the time between theaddition of cryoprotectant to the cells and the time the product isplaced in an ultra-cold freezer. The devices and methods describedherein can reduce bag manipulation time and therefore increaseefficiency and productivity of a technologist. The devices and methoddescribed herein can reduce physical stresses and discomfort for theprocessing technologist. The cell viability also is increased, leadingto higher quality of products for patients. Accordingly, patientsatisfaction is increased while patient stress is decreased. Anadvantage for payers (e.g., insurance payers) is increased reliabilityand decreases in payout due to higher quality products.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described herein. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription, drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is side view of a clamping device in accordance with someembodiments provided herein.

FIG. 2 is a perspective view of the clamping device of FIG. 1, inaccordance with some embodiments provided herein.

FIG. 3 is a perspective view of a clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 4 is a bottom view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 5 is a top view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 6 is a front view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 7 is a back view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 8 is a first side view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 9 is a second view of the clamp element of FIGS. 1 and 2, inaccordance with some embodiments provided herein.

FIG. 10A-10D show a method of using a clamping device with a cryogenicfreezing bag, in accordance with some embodiments provided herein.

Like reference numbers represent corresponding parts throughout.

DETAILED DESCRIPTION

This document relates to methods and materials for improving the removalof gas from cryogenic freezing bags. For example, this documentdescribes methods and devices for restricting air paths within thecryogenic freezing bag.

When processing hematopoietic progenitor cells (HPC) collections,apheresis HPC(A), or bone marrow HPC(M), it is important to remove anyair that may be trapped in the cryogenic freezing bag after the finalproduct has been added to the bag, and before cryopreservation of thefinal product. It is very important to work methodically and efficientlyafter mixing the blood product with the cryoprotectant and the mixtureis put into a cryogenic freezing bag. The cryoprotectant mixture cancontain Dimethyl sulfoxide (DMSO), which is toxic to cells at roomtemperature and upon extended exposure if not frozen at cryogenictemperature (≤−150° C.).

After the cryogenic freezing bag has been frozen at cryogenictemperature, the freezing bag becomes brittle. This brittleness of thefreezing bag when frozen makes it important to remove large pockets ofair from the bag before cryopreservation to avoid bag breakage. Thepresence of air pockets in the bag after cryopreservation increases therisk of frozen bag breakage if slight pressure is applied over the airpocket when handling the frozen bag for inspection in preparation forproduct release for thawing and infusion. In a case of a bag breakage, avital unreplaceable product may be lost, directly impacting patientcare.

Therefore, by more efficiently and effectively removing gas from thecryogenic freezing bag, cell viability can be increased.

Referring to FIGS. 1 and 2, a clamping device 10 can include a clampelement 100 coupled to a hemostat 12.

Hemostat 12 can include a set of handles 14 a and 14 b that a user canuse to grip hemostat 12 that extend to tips 18 a and 18 b, respectively.Handles 14 a and 14 b, are coupled together via a pivot 16, such thatactuation of handles 14 a and 14 b causes actuation of tips 18 a and 18b. In some cases, handles 14 a and 14 b can include a locking mechanism15 a and 15 b that allows the user to adjust the clamping force of thehemostat 12. For example, the locking mechanism 15 a and 15 b can be aseries of interlocking teeth.

Clamp element 100 can include two clamp elements 100 a and 100 b. Insome cases, clamp elements 100 a and 100 b can be removably coupled totips 18 a and 18 b of hemostat 12. In some cases, clamp elements 100 aand 100 b can be substantially identical, such that a single design forclamp element 100 can be used for both clamp elements. Such aconfiguration can increase ease of use. In some cases, clamp elements100 a and 100 b can be single use, disposable pieces. In some cases,clamp elements 100 a and 100 b are disposable, while hemostat 12 isreusable. In some cases, clamp elements 100 a and 100 b are reusable. Insome cases, clamp elements 100 a and 100 b can be integral with hemostat12. For example, a clamping device can include a handle, a pivotingmechanism, and a clamping portion opposite the handle.

Referring to FIGS. 3-9, the clamp element 100 can include a couplingportion 102, a first side arm 108, and a second side arm 110.

Coupling portion 102 can define a central opening 104 along a distalportion, and a coupling aperture 106 on a proximal portion. Centralopening 104 can provide access for a tube extending from a cryogenicfreezing bag, such that the tube is not clamped to allow for removal ofgas. Coupling aperture 106 can couple clamp element 100 to hemostat 12(shown in FIGS. 1 and 2). In some cases, aperture 106 can extend all theway through coupling portion 102 to central opening 104. In some cases,aperture 106 can extend partially through coupling portion 102. In somecases, aperture 106 can extend through coupling portion 102 at an angleoffset from a longitudinal axis of the coupling portion 102. In somecases, the angle of aperture 106 can aid in clamping a cryogenicfreezing bag. Optionally, aperture 106 can include a grip material, ortexture, to aid in coupling and/or locking clamp element 100 to ahemostat 12. In some cases, aperture 106 can include a stoppingmechanism. In some cases, when coupling clamp element 100 to hemostat12, clamp element 100 can be pushed onto hemostat 12 until a stoppingpoint is reached, such as stopping mechanism.

First side arm 108 and second side arm 110 can include extend outwardlyfrom coupling portion 102 in substantially opposite directions (e.g.,approximately 180 degrees from one another). In some cases, first sidearm 108 and second side arm 110 can extend outwardly from couplingportion 102 in different directions, such that an angle A is definedbetween first side arm 108 and second side arm 110. Angle A can be about110 degrees to about 180 degrees. In some cases, first side arm 108 andsecond side arm 110 can extend away from coupling portion 102 such thatfirst side arm 108 and second side arm 110 curve away from couplingportion 102. In some cases, first side arm 108 and second side arm 110are curved along a length of first side arm 108 and second side arm 110.In some cases, first side arm 108 and second side arm 110 can have a“birdwing” shape.

First side arm 108 can define a recess 112, and second side arm 110 candefine a protrusion 114 that is complementary to recess 112. Forexample, protrusion 114 is complementary to recess 112 such that arecess 112 and protrusion 114 of a first clamp element 100 a can mate toa protrusion 114 and a recess 112 of a second clamp element 100 b. Insome cases, protrusion 114 and recess 112 can couple to create a seal.In some cases, angle A between first side arm 108 and second side arm110 provides a first clamp element 100 a and a second clamp element 100b that are substantially identical while allowing a recess 112 andprotrusion 114 of a first clamp element 100 a to mate with a protrusion114 and a recess 112 of a second clamp element 100 b.

Recess 112 and protrusion 114 can be triangular, circular, rectangular,oblong, or other complementary shape with one another. In some cases,first side arm 108 and second side arm 110 can be made of a firstmaterial (e.g., a substantially rigid plastic), while protrusion 114 anda portion of first arm 108 that defines recess 112 can be made of asecond material (e.g., rubber, silicone, etc.).

In some cases, clamp element 100 can include a locking mechanism. Forexample, a locking mechanism can lock a first clamp element 100 a to asecond clamp element 100 b. In some cases, the locking mechanism can aidin preventing movement of the clamp elements 100 a and 100 b whenclamped on a cryogenic freezing bag.

In some cases, a specific orientation and/or arrangement of couplingportion 102, first side arm 108, and second side arm 110 can bedifferent than shown in FIGS. 3-9 to allow for clamping of a cryogenicbag with a different shape and/or configuration.

Referring to FIGS. 10A-10D, a method of using a clamping device 10 witha cryogenic freezing bag 20 is shown. In some cases, cryogenic freezingbag 20 can include a chamber 22, a tube 24, and one or more spike ports26 a and 26 b. Chamber 22 can house a sample and/or a cryoprotectant.Tube 24 can be coupled to a syringe 28 to aid in the removal of gas fromcryogenic freezing bag 20. Spike ports 26 a and 26 b can be used tointroduce and/or remove a sample and/or a cryoprotectant.

As shown in FIG. 10A, cryogenic freezing bag 20 can be inverted, suchthat a sample 22 a inside chamber 22 moves toward spike ports 26 a and26 b, and tube 24. Clamping device 10 can be clamped to cryogenicfreezing bag 20. In some cases, cryogenic freezing bag 20 is tapped(e.g., with a finger of a user) in order to remove gas from spike ports26 a and 26 b, prior to clamping. In some cases, first side arm 108 andsecond side arm 110 of first and second clamp elements 100 a and 100 bcan extend around spike ports 26 a and 26 b creating a seal betweenspike ports 26 a and 26 b and chamber 22. In some cases, tube 24 canextend through central opening 104 of first and second clamp elements100 a and 100 b, such that tube 24 remains fluidly coupled to chamber22. In some cases, clamping device 10 can be locked to maintain theclamped position (e.g., via a locking mechanism 15 a and 15 b onhemostat 12, as shown in FIG. 2, and/or via a locking mechanism on clampelements 100 a and 100 b).

As shown in FIG. 10B, clamping device 10 is clamped on cryogenicfreezing bag 20 and cryogenic freezing bag 20 is turned right side up,such that sample 22 a in chamber 22 is moved away from spike ports 26 aand 26 b, and tube 24. In some cases, hemostat 12 can be hung from astand (e.g., by handles 14 a and 14 b) to allow a user to use both handsto manipulate cryogenic freezing bag 20.

As shown in FIG. 10C, cryogenic freezing bag 20 can be manipulated by auser with one hand while removing gas from the cryogenic freezing bag 20using syringe 28.

As shown in FIG. 10D, gas has been removed from cryogenic freezing bag20, and cryogenic freezing bag 20 can be prepped for placement in acryogenic freezer. For example, tube 24 can be sealed and cut.

While this specification contains many specific implementation details,these should not be construed as limitations on the scope of anyinvention or of what may be claimed, but rather as descriptions offeatures that may be specific to particular embodiments of particularinventions. Certain features that are described in this specification inthe context of separate embodiments can also be implemented incombination in a single embodiment. Conversely, various features thatare described in the context of a single embodiment can also beimplemented in multiple embodiments separately or in any suitablesubcombination. Moreover, although features may be described herein asacting in certain combinations and even initially claimed as such, oneor more features from a claimed combination can in some cases be excisedfrom the combination, and the claimed combination may be directed to asubcombination or variation of a subcombination.

Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. In certain circumstances, multitasking and parallel processingmay be advantageous. Moreover, the separation of various system modulesand components in the embodiments described herein should not beunderstood as requiring such separation in all embodiments, and itshould be understood that the described program components and systemscan generally be integrated together in a single product or packagedinto multiple products.

Particular embodiments of the subject matter have been described. Otherembodiments are within the scope of the following claims. For example,the actions recited in the claims can be performed in a different orderand still achieve desirable results. As one example, the processdepicted in the accompanying figures do not necessarily require theparticular order shown, or sequential order, to achieve desirableresults. In certain implementations, multitasking and parallelprocessing may be advantageous.

What is claimed is:
 1. A method of removing a gas from a cryogenic freezing bag, comprising: removably coupling a first clamping element of a clamping device to a first tip of a hemostat of the clamping device; removably coupling a second clamping element of the clamping device to a second tip of the hemostat of the clamping device; clamping the clamping device on the cryogenic freezing bag; and removing the gas from the cryogenic freezing bag through an opening defined by the cryogenic freezing bag.
 2. The method of claim 1, wherein removably coupling the first and second clamping elements to the first and second tips of the hemostat comprises: i) removably coupling a first coupling aperture to the first tip of the hemostat, and ii) removably coupling a second coupling aperture to the second tip of the hemostat, the first coupling aperture defined by a first coupling portion of the first clamping element, and the second coupling aperture defined by a second coupling portion of the second clamping element.
 3. The method of claim 2, wherein the opening is a central opening and clamping the clamping device on the cryogenic freezing bag comprises sealing a first opening of the cryogenic freezing bag.
 4. The method of claim 3, wherein the first opening is a spike port of the cryogenic freezing bag.
 5. The method of claim 3, further comprising moving a sample within a chamber of the cryogenic freezing bag toward the first opening by inverting the cryogenic freezing bag prior to clamping the clamping device on the cryogenic freezing bag.
 6. The method of claim 3, wherein sealing the first opening of the cryogenic freezing bag comprises extending a first side arm of the first clamping element and a third side arm of the second clamping element around the first opening, the first side arm extending from the first coupling portion in a first direction, and the third side arm extending from the second coupling portion in a third direction.
 7. The method of claim 6, wherein clamping the clamping device on the cryogenic freezing bag comprises mating a second protrusion defined by the third side arm with a first recess defined by the first side arm.
 8. The method of claim 7, wherein clamping the clamping device on the cryogenic freezing bag comprises sealing a second opening of the cryogenic freezing bag.
 9. The method of claim 8, wherein sealing the second opening of the cryogenic freezing bag comprises extending a second side arm of the first clamping element and a fourth side arm of the second clamping element around the second opening, the second side arm extending from the first coupling portion in a second direction, and the fourth side arm extending from the second coupling portion in a fourth direction.
 10. The method of claim 9, wherein clamping the clamping device on the cryogenic freezing bag comprises mating a first protrusion defined by the second side arm with a second recess defined by the fourth side arm.
 11. The method of claim 2, wherein the first clamping element and the second clamping element are pivotally coupled along the first and second coupling portions.
 12. The method of claim 10, further comprising mating of the first protrusion with the second recess and the second protrusion with the first recess by moving a first handle defined by the first coupling portion towards a second handle defined by the second coupling portion.
 13. The method of claim 12, wherein moving the first handle towards the second handle comprises pivotally actuating the first and second coupling portions.
 14. The method of claim 1, wherein removing the gas from the cryogenic freezing bag comprises using the opening to provide access for a tube in fluid connection with and extending from the cryogenic freezing bag.
 15. The method of claim 14, wherein removing the gas from the cryogenic freezing bag comprises coupling a syringe to the tube to aid in the removal of the gas.
 16. The method of claim 14, further comprising sealing the tube after removing the gas from the cryogenic freezing bag.
 17. The method of claim 14, further comprising extending the tube through a central opening defined by a coupling portion at a distal end of the clamping device.
 18. The method of claim 1, further comprising adjusting a clamping force of the clamping device by adjusting a locking mechanism of the hemostat.
 19. The method of claim 18, further comprising locking the clamping device to maintain a clamped position by locking the locking mechanism of the hemostat.
 20. The method of claim 1, further comprising hanging the cryogenic freezing bag by a handle of the clamping device after removing the gas from the cryogenic freezing bag. 